RESUMO
Depression is one of the world's most common and mentally disabling illnesses. Post-partum depression is a subtype of depression that affects one in seven women worldwide. Successful pharmacological treatment must consider the consequences for both, since the mother-child bond is fundamental for the well-being of both mother and infant as well as the general development of the newborn. Changes in maternal physiology and/or behavior can significantly influence the development of breastfed infants. Ketamine has been extensively studied for use as an antidepressant due to its mixed mechanisms of action. Safety and efficacy studies in the cardiovascular and urinary systems of a lactating postpartum depression animal model are essential for contributing toward ketamine's clinical use in the respective patient population. Thus, this project aimed to study the implications of postpartum maternal exposure to ketamine during lactation on the cardiovascular system of female rats submitted to the depression induction model by maternal separation. This model promotes depressive effects through stress caused by the interruption of mother-infant bond early in the offspring's life. To achieve depression, each dam was separated from her offspring for 3 h per day, from post-natal day 2 (PND2) to PND12. Experimental groups received daily treatment with either 5, 10, or 20 mg/kg of ketamine intraperitoneally during the lactation period, from PND2 to PND21. Behavioral tests consisted of the maternal and aggressive maternal behavior tests, the olfactory preference test, and the forced swim test. A technique for the detection of catecholamines and indoleamines in the heart muscle was developed for the experimental model groups. The histopathological evaluation was performed on these animals' cardiac muscles and urinary bladders. Our findings suggest that ketamine is safe for use in postpartum depression and does not induce cardiovascular and/or urinary systems toxicity.
RESUMO
Immunoglobulin A nephropathy is the main cause of glomerulonephritis globally and an important aetiology of end-stage renal disease in children. It has been considered an autoimmune disease that can lead to the production of autoantibodies against abnormal IgA1 and formation of immune complexes. These autoantibodies and immune complexes deposit in the glomeruli, resulting in renal injury. At the beginning of IgA nephropathy course, most patients are asymptomatic and the first clinical manifestations in children are macroscopic hematuria and proteinuria. The diagnosis is defined by the detection of IgA mesangial deposits in kidney biopsy using immunofluorescence techniques. The Oxford MEST-C score is the most used classification to associate histological findings and clinical outcomes, being validated for application in children. Recommended treatment options are antihypertensive and antiproteinuric therapy, corticosteroids, immunosuppressive agents, and other non-pharmacological approaches. There is no ideal prognosis indicator but new perspectives are in science's scope to find possible biomarkers of the disease through OMICS's research. This review aims to summarize and to up-to-date the scientific literature on paediatric IgA nephropathy, focusing on pathophysiology, clinical findings, histopathology, current treatment, prognosis, and future perspectives.
Assuntos
Glomerulonefrite por IGA , Glomerulonefrite , Pediatria , Criança , Glomerulonefrite/patologia , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/terapia , Humanos , Imunoglobulina A , Glomérulos Renais/patologiaRESUMO
BACKGROUND: Depression is one of the most common mentally debilitating diseases in the world. Ketamine has been recently identified as a potential novel antidepressant. Further animal model evaluations of the use of ketamine as an antidepressant are necessary to determine safety parameters for clinical use. Therefore, the objective of this study was to perform toxicological tests of prolonged treatment using three different doses of ketamine in adult male rats. METHODS: The animals were divided into four groups: three treated with 5, 10 or 20 mg/kg of ketamine and a control group treated with saline solution. Intraperitoneal route of treatment was administered daily for 3 weeks. Body weight, water and food intake were measured once a week, as well as evaluation of the functional observational battery, which includes methodic monitoring of motor activity, motor coordination, behavioral changes, and sensory/motor reflex responses. Upon completion of treatment period, all animals were euthanized by decapitation followed by immediate collection of samples, which included brain structures and blood for neurochemical, hematological and biochemical analyses. RESULTS: Rats treated with the highest tested dosage (20 mg/kg) of ketamine had lower weight gain in the 1st and 2nd weeks of treatment and all experimental groups had measurable alterations in the serotoninergic system. CONCLUSIONS: Our data indicate that the alterations observed are minor and due to a predicted mechanism of action, which implies that ketamine is a promising drug for repurposing as an antidepressant.
Assuntos
Antidepressivos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Ketamina/administração & dosagem , Animais , Antidepressivos/farmacologia , Antidepressivos/toxicidade , Depressão/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ketamina/farmacologia , Ketamina/toxicidade , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Testes de ToxicidadeRESUMO
Varenicline is a synthetic chemical substance produced from the alkaloid cytisine, used for smoking treatment, which acts as a partial agonist for α4ß2 and α3ß4 nicotinic cholinergic receptors and as a total agonist for α7 receptor. While there are studies regarding varenicline's non-smoking-related effects, as in treatment for drug dependence, there are no studies in the literature evaluating the long-term toxicity of varenicline through a physiological approach. Thus, the aim of this study was to evaluate possible toxicity through haematological, biochemical and anatomopathological parameters of prolonged exposure (30 days) to varenicline in rats. Three doses of varenicline were used: 0.03 (therapeutic dose for human beings), 0.1 and 0.3 mg/kg orally (gavage). Body-weight, water and food intake were measured weekly during treatment. On the 30th treatment day, blood and various organs were collected for haematological, biochemical and anatomopathological evaluations. The results show a decrease in some biochemical parameters in animals from the 0.1 and 0.3 mg/kg group, although the values are within the normal range of the species. There were no changes in the other evaluations performed. Together, these data indicate that prolonged exposure of rats to different doses of varenicline was not able to alter haematological, biochemical and anatomopathological parameters.